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Ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, remdesivir and favipiravir tested against 2019-nCoV in vitro

Zac

Well-known member
Chinese team finds drugs effectively inhibit new coronavirus in vitro [cell culture, not in animal]


...they evaluated five FDA-approved drugs, ribavirin, penciclovir, nitazoxanide, nafamostat and chloroquine, and two The efficacy of a well-known broad-spectrum antiviral drug, remdesivir (GS-5734) and favipiravir (T-705), against 2019-nCoV in vitro.

Nitazoxanide is an antiprotozoal drug that has the potential to combat a wide range of viruses, including human and animal coronaviruses, and inhibits 2019-nCoV at low micromolar concentrations (EC 50 = 2.12 μM) . It is recommended to further evaluate the effectiveness of the drug in vivo against 2019-nCoV infection. [Comment: repeated 500 mg BID administration yields 9 μM blood serum concentration, Kucers' Antibiotic reference. Nitazoxanide also has immunomodulary and anti-inflammatory properties and studies found 500 mg BID for 5 days had side effects similar to placebo.]


It is worth noting that two compounds, remdesivir and chloroquine, can effectively block 2019-nCoV infection at micromolar concentrations, with EC 50 values ​​of 0.77 μM and 1.13 μM, respectively; the selectivity index of the two is used to judge the drug effect (The larger the index, the larger the safety range) are (Figure 1a, b) .


Remdesivir has recently been recognized as a promising antiviral drug that can fight multiple RNA virus (including SARS / MERS-CoV) infections in cultured cells, mice and non-human primate models. The drug is currently undergoing clinical research to treat Ebola virus infection. Remdesivir is an adenosine analog that integrates into the nascent viral RNA strand, leading to the termination of pre-mature. This new study found that remdesivir works after the virus enters the cells (Figure 1c, d) , consistent with its well-known antiviral mechanism as a nucleotide analog. In addition, preliminary data show that remdesivir can also effectively inhibit human cell lines sensitive to 2019-nCoV.


Chloroquine is a widely used antimalarial and autoimmune disease drug and has recently been reported as a potential broad-spectrum antiviral drug. Chloroquine is known to prevent viral infections by increasing the endosome pH required for virus / cell fusion and interfering with the glycosylation of SARS-CoV cell receptors. This new study confirms that Chloroquine plays a role during the virus invasion phase and after virus invasion of Vero E6 cells infected with 2019-nCoV (Figure 1c , d) . In addition to its antiviral effect, Chloroquine also has an immunomodulatory effect, which can synergistically enhance its antiviral effect in vivo. Chloroquine is widely distributed throughout the body, including the lungs, after oral administration. The EC 90 value of 2019-nCoV in Chloroquine anti-Vero E6 cells is 6.90 μM, which is clinically achievable, which was confirmed in the plasma of patients with rheumatoid arthritis administered 500 mg. Chloroquine is a cheap and safe drug that has been used for more than 70 years, so it may be clinically applicable to 2019-nCoV. [Comment: chloroquine has narrow therapeutic range and less than benign side effect profile]


In summary, the study shows that remdesivir and chloroquine are effective in controlling 2019-nCoV infection in vitro. Because these compounds have been used in patients with safety records and have proven effective against a variety of diseases, researchers have suggested that the two drugs should be evaluated in patients infected with the new coronavirus.

https://translate.google.com/transla...mp;prev=search https://mp.weixin.qq.com/s/zN1FR0InIOjr-9EguryOAQ


 
Please also see:


Drug Discov Ther. Discovering drugs to treat coronavirus disease 2019 (COVID-19)

Favipiravir, an anti-influenza drug against life-threatening RNA virus infections

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Also called Favipiravir it is being trialed in China already.
https://www.nature.com/articles/d41573-020-00016-0

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China says Japan-developed drug Avigan works against coronavirus


Positive reception by Chinese government contrasts with reservations in Japan


https://asia.nikkei.com/Spotlight/Co...st-coronavirus
 
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